crossing96/oncoscreening huggingface dataset:
Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania.	Recently, chronic Aristolochia poisoning was found responsible for the aetiology of Balkan endemic nephropathy (BEN) in Croatia, Serbia, and Bosnia, and diet was the likely route of exposure to aristolochic acid (AA). BEN, often associated with an increased incidence of upper urinary tract carcinoma (UUC), also affects residents of certain rural villages in Romania. AA is a nephrotoxin and human carcinogen that forms DNA adducts after metabolic activation, which induce characteristic TP53 mutations in urothelial tumours. Here we present the first evidence linking AA exposure to UUC in residents of an endemic region in the Romanian Mehedinti County. DNA was extracted from kidney and tumour tissue of seven patients who underwent nephroureterectomy for UUC and resided in BEN villages (endemic group). Five patients with UUC from nonendemic villages served as controls. AA-DNA adducts (7-(deoxyadenosin-N(6) -yl)-aristolactam I), established biomarkers of AA exposure, were identified by (32)P-postlabelling in renal DNA of six patients from the endemic group and in one of the nonendemic group (adduct levels ranged from 0.3 to 6.5 adducts per 10(8) nucleotides). Additionally, an A to T transversion in TP53, a base substitution characteristic of AA mutagenic activity was found in urothelial tumour DNA of one patient from the endemic group. Our results provide a molecular link to the cause of urothelial tumours in BEN regions of Romania indicating that AA is the common aetiological agent for BEN across its numerous geographical foci.	bladder
JR6, a new compound isolated from Justicia procumbens, induces apoptosis in human bladder cancer EJ cells through caspase-dependent pathway.	ETHNOPHARMACOLOGICAL RELEVANCE: Numerous efforts have been conducted in searching for effective agents against cancer, in particular from herbal medicines. Justicia procumbens is a traditional herbal remedy which was produced in the south-western and southern provinces of China and Taiwan province used to treat fever, pain, and cancer. Here, we identified a new compound 6'-hydroxy justicidin A (JR6) from Justicia procumbens, which showed obvious anti-cancer effects. MATERIALS AND METHODS: The cytotoxicity activity was assayed using MTT and SRB. Intracellular ROS visualization and quantification were acquired by using a laser scanning confocal microscopy. Apoptosis was measured using a propidium iodide (PI) apoptosis detection kit by flow cytometry. Activation of caspases (caspase-3, caspase-8, and caspase-9) was evaluated respectively using GloMax luminescence detector and Caspase-Glo 3,8,9 assay kits. Loss of mitochondrial membrane potential was observed by microscopy using JC-1 dye. Quantitative real-time PCR analysis was employed to detect the expression of protein associated with cell death. RESULTS: JR6 remarkably inhibited growth in human bladder cancer EJ cells by decreasing cell proliferation, reduced the SOD activity, increased the content of reactive oxygen species (ROS), and induced apoptosis. Activation of caspase-8, caspase-9, and the subsequent activation of caspase-3 indicated that JR6 may be inducing intrinsic and extrinsic apoptosis pathways. Caspase-3, caspase-8, and caspase-9 inhibition rendered this extract ineffective, thus JR6-induced apoptosis is caspase-dependent. JR6 also disrupted the mitochondrial membrane potential (Δψm) and unregulated the Bax and p53 expressions in EJ cells. CONCLUSION: These observations suggest that JR6 induce apoptosis through caspase-dependent pathway in human bladder cancer EJ cells, emphasizing the importance of this traditional medicine and thus presents a potential novel alternative to bladder cancer therapy.	bladder
Narrow band imaging diagnosis of bladder cancer: systematic review and meta-analysis.	What's known on the subject? and What does the study add? In recent years, more attention has focused on the role of narrow band imaging (NBI) in bladder cancer detection and NBI technology has spread rapidly. It is an important method for diagnosing new or recurrent bladder cancer. But its diagnostic accuracy is still uncertain. This paper summarizes the diagnostic accuracy of NBI in bladder cancer and compares NBI with white light imaging. The results show that NBI cystoscopy significantly improves the detection accuracy in bladder cancer, compared with white light imaging. However, some limitations still exist. Multicentre randomized studies are recommended to determine whether the visual advantages of NBI can translate into real therapeutic benefit for individual patients. OBJECTIVE: • To assess the test performance and clinical effectiveness of narrow band imaging (NBI) cystoscopy compared with white light imaging (WLI) cystoscopy in people suspected of new or recurrent bladder cancer. METHODS: • Literature on NBI cystoscopy in the diagnosis of bladder cancer was searched in PubMed, EMBASE, Cochrane Library, MEDLINE and CNKI, with hand searching of relevant congress abstracts and journals. • The literature was selected according to inclusion and exclusion criteria. The Meta-DiSc1.4 software was used to review management and analysis. RESULTS: • Eight studies including 1022 patients assessed test performance. • On a per-person analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of NBI and WLI were respectively 0.943 (95% CI 0.914-0.964) and 0.848 (95% CI 0.803-0.885), 0.847 (95% CI 0.812-0.878) and 0.870 (95% CI 0.831-0.903), 7.038 (95% CI 3.357-14.754) and 6.938 (95% CI 2.052-23.465), 0.054 (95% CI 0.012-0.237) and 0.181 (95% CI 0.091-0.361), and 185.32 (95% CI 45.714-751.26) and 42.931 (95% CI 8.088-227.88). • The area under the curve and Q* of NBI and WLI were respectively 0.9781 and 0.8944, and 0.9337 and 0.8253. • For the characterization of carcinoma in situ, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of NBI were 0.927 (95% CI 0.878-0.960), 0.768 (95% CI 0.730-0.802), 4.545 (95% CI 2.820-7.325), 0.125 (95% CI 0.051-0.304) and 48.884 (95% CI 15.642-152.77) on a per-person analysis. • The area under the curve and Q* were 0.9391 and 0.8763. CONCLUSION: • NBI is an effective method for the identification of abnormal lesions including carcinoma in situ and can provide higher diagnostic precision of bladder cancer than WLI.	bladder
Retrospective analysis of clinical outcomes with neoadjuvant cisplatin-based regimens for muscle-invasive bladder cancer.	"BACKGROUND: The benefit of neoadjuvant methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC) for muscle-invasive bladder cancer (MIBC) has been prospectively demonstrated in a phase III study. Extrapolating from comparative data in the metastatic setting, platinum doublets such as cisplatin-gemcitabine (CG) have been adopted. We sought to compare clinical outcomes in patients treated for MIBC with neoadjuvant CG and MVAC at our institution. PATIENTS AND METHODS: Patients with MIBC were identified from a prospectively maintained registry. Clinicopathologic information and clinical outcome data were obtained directly from the registry. When available, pharmacy records were reviewed to ascertain the use of growth factors and chemotherapy dose intensity (DI). Survival was compared in subgroups divided by the regimen of chemotherapy rendered (ie, CG vs. MVAC) using the Kaplan-Meier method. RESULTS: Median overall survival (OS) in the overall cohort (N = 61) was 23 months. OS was improved in patients receiving either MVAC or CG chemotherapy compared with patients receiving ""other"" chemotherapy (35.3 vs. 16.3 months; P = .055). Although the median OS associated with neoadjuvant CG numerically exceeded the survival associated with neoadjuvant MVAC (104.3 and 21.8 months, respectively), this was not statistically significant (P = .73). Pathologic downstaging predicted improved OS with both neoadjuvant CG and MVAC, and the rates of downstaging were similar with both regimens. CONCLUSIONS: Although warranting prospective validation, our data suggest that CG is a possible alternative neoadjuvant approach to traditional regimens such as MVAC for patients with MIBC."	bladder
Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR.	BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio=7.4 (95% confidence interval: 3.4-15.9), P<0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.	bladder
Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy.	Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Data on the oncological outcomes in patients undergoing salvage cystectomy for recurrent disease following bladder-sparing treatment is limited and mostly based on case reports. We present the clinical outcomes and prognostic factors in patients undergoing radical cystectomy for recurrent disease following partial cystectomy with long-term follow-up. OBJECTIVE: To report the clinical outcomes and prognostic factors in patients undergoing salvage radical cystectomy (sRC) for recurrent urothelial carcinoma (UC) of the bladder following partial cystectomy (PC). PATIENTS AND METHODS: Between 1971 and 2011, a total of 2290 patients underwent radical cystectomy for UC of the bladder, including 72 patients (3.1%) who underwent sRC following PC. Clinical and pathological data at the time of both PC and sRC were collected. Median follow-up time after sRC was 10.9 years. Overall survival and recurrence-free survival were the primary outcomes of interest. Univariate and multivariate analyses were performed to identify prognostic factors after sRC. RESULTS: The median time from PC to sRC was 1.6 years. Median age at sRC was 64 years. Peri-operative mortality was 2.8%. After sRC, 44 patients (61.2%) had pathologically organ-confined disease, 14 patients (19.4%) extravesical disease and 14 patients (19.4%) lymph node positive disease. Five-year recurrence-free survival and overall survival following sRC were 56% and 41%, respectively. On multivariate analysis, the presence of pathological tumor stage ≥pT3a (hazard ratio 6.86, P < 0.001) and the presence of lymph node metastases (hazard ratio 8.78, P < 0.001) were associated with increased risk of recurrence after sRC. CONCLUSIONS: sRC can provide prolonged survival following failure of PC. Prognosis, however, is highly dependent on pathological tumour stage and nodal status at sRC. Only 15% of patients with locally advanced recurrent disease were salvaged by sRC.	bladder
Association of human herpes, papilloma and polyoma virus families with bladder cancer.	The aim of the present study was to assess the possible etiologic role of human papillomavirus (HPV), human herpes virus (HHV) and the human polyoma virus families (BKV and JCV) in the tumourigenesis of bladder cancer. Thirty biopsy specimens from patients with different grades and stages of bladder cancer, who underwent transurethral bladder cancer resection, and 30 normal bladder mucosa specimens were analysed using polymerase chain reaction (PCR) for the detection of the above three virus family members. The presence of HPV was determined in all specimens with nested PCR and real-time quantitative PCR. All cancerous specimens, including the control group, were found to be negative both by PCR and real-time qPCR for the presence of HPV DNA, whilst all samples examined by PCR tested negative for the presence of HSV-1,2 Varicella zoster virus and HSV-7 DNA. Cytomegalovirus, HHV-6 and HHV-8 exhibited similar incidence in sample positivity in both cancerous and healthy tissues. EBV showed a higher prevalence in bladder cancer specimens compared to healthy tissue (p = 0.048), whilst BKV and JCV were detected only in tumour samples. The presence of EBV in a significant proportion of bladder tumours indicates the etiological role of this virus in cancer tumourigenesis.	bladder
NMR-based metabolomics study of canine bladder cancer.	Bladder cancer is one of the leading lethal cancers worldwide. With the high risk of recurrence for bladder cancer following the initial diagnoses, lifelong monitoring of patients is necessary. The lack of adequate sensitivity and specificity of current noninvasive monitoring approaches including urine cytology, other urine tests, and imaging, underlines the importance of studies that focus on the detection of more reliable biomarkers for this cancer. The emerging area of metabolomics, which deals with the analysis of a large number of small molecules in a single step, promises immense potential for discovering metabolite markers for screening and monitoring treatment response and recurrence in patients with bladder cancer. Since naturally-occurring canine transitional cell carcinoma of the urinary bladder is very similar to human invasive bladder cancer, spontaneous canine transitional cell carcinoma has been applied as a relevant animal model of human invasive transitional cell carcinoma. In this study, we have focused on profiling the metabolites in urine from dogs with transitional cell carcinoma and healthy control dogs combining nuclear magnetic resonance spectroscopy and statistical analysis methods. (1)H NMR-based metabolite profiling analysis was shown to be an effective approach for differentiating samples from dogs with transitional cell carcinoma and healthy controls based on a partial least square-discriminant analysis of the NMR spectra. In addition, there were significant differences in the levels of six individual metabolites between samples from dogs with transitional cell carcinoma and the control group based on the Student's t-test. These metabolites were selected to build a separate partial least square-discriminant analysis model that was then used to test the classification accuracy. The result showed good classification between transitional cell carcinoma and control groups with the area under the receiver operating characteristic curve of 0.85. The sensitivity and specificity of the model were 86% and 78%, respectively. These results suggest that urine metabolic profiling may have potential for early detection of bladder cancer and of bladder cancer recurrence following treatment, and may enhance our understanding of the mechanisms involved.	bladder
[Role of autophagy in quercetin-induced apoptosis in human bladder carcinoma BIU-87 cells].	OBJECTIVE: To explore the role of autophagy in quercetin (Que)-induced apoptosis in human bladder carcinoma BIU-87 cells in vitro. METHODS: To determine the proliferative inhibition by MTT colorimetric assay after treating BIU-87 cells with quercetin at various concentrations. To identify autophagy and apoptosis in the BIU-87 cells after Que treatment by monodansylcadaverin (MDC) and Hoechst 33258 fluorescent staining, respectively. To examine the cytotoxic effect of Que and influence of autophagy on apoptosis by studying LDH leakage rate and flow cytometry, after blocking the autophagy with 3-methlyadenine (3-MA), a specific autophagy inhibitor. RESULTS: There was an obvious inhibitory effect of Que on the proliferation of BIU-87 cells in a time- and dose-dependent manner. The inhibition rate of BIU-87 cells after 200 µmol/L Que treatment for 72 hours was 89.2%. Autophagy and apoptosis were induced and detected in Que-treated BIU-87 cells and autophagy occurred earlier than apoptosis. The apoptosis peak became much higher after the autophagy was blocked. Whenever the autophagy was blocked before or after Que treatment, the Que-induced cytotoxicity in BIU-87 cells was enhanced. CONCLUSIONS: Quercetin significantly inhibits the proliferation of BIU-87 cells, and the autophagy is induced earlier than apoptosis. In the process of Que-induced apoptosis of BIU-87 cells, autophagy may play a protective role at the initiation phase, delay apoptosis and reduce the Que-induced death of BIU-87 cells.	bladder
Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A.	We used gene expression profiling to identify inflammatory cytokines that correlate with bladder cancer development. Gene expression profiles of the tissue samples were investigated using cDNA microarrays that contained 103 non-muscle invasive bladder cancers (NMIBC), 62 muscle invasive bladder cancers (MIBC), 58 samples of histologically normal-looking surrounding tissues, and 10 normal, healthy subjects who served as the control cohort for comparison. We grouped the data-sets according to biological characterizations and focused on immune response genes with at least 2-fold differential expression in MIBC vs. controls. The experimental data-set identified 36 immune-related genes that were significantly altered in MIBC samples. In addition, 10 genes were up-regulated and 26 genes were down-regulated in MIBC samples compared with the normal tissues. Among the 10 up-regulated molecules examined, the capacity for both wound-healing migration and invasion was enhanced in response to IL-5, IL-20, and IL-28A in bladder cancer cell lines (253J and EJ cells), compared with untreated cells. The expression levels of IL-5, IL-20, and IL-28A were increased in patients with MIBC. All 3 cytokines and their receptors were produced in bladder cancer cell lines, as determined by real-time PCR, immunoblot analysis and confocal immunofluorescence. Up-regulation of MMP-2 and MMP-9 was found after IL-5, IL-20, and IL-28A stimulation in both cell types. Moreover, an EMSA assay showed that treatment with IL-5, IL-20, and IL-28A induced activation of the transcription factors NF-κB and AP-1 that regulate the MMP-9 promoter. Finally, activation of MAPK and Jak-Stat signaling was observed after the addition of IL-5, IL-20, and IL-28A to bladder cancer cells. This study suggests the presence of specific inflammatory cytokine (IL-5, IL-20, and IL-28A)-mediated association in bladder cancer development. All 3 cytokines may be important new molecular targets for the modulation of migration and invasion in bladder cancer.	bladder
A newly developed double lumen microballoon catheter with a side hole: initial experience of intraarterial infusion chemotherapy and/or embolization.	PURPOSE: To introduce a newly developed double lumen microballoon catheter with a side hole for intraarterial infusion chemotherapy and/or embolization. METHODS AND MATERIALS: Seven patients with malignant tumors, for whom superselective catheterization was considered difficult or had failed, underwent intraarterial infusion chemotherapy and/or embolization with the 3.3-Fr microballoon catheter. The catheter has a double lumen and a side hole to facilitate infusion from the proximal end of the balloon. The balloon was placed on the distal side of the target artery branching site. Inflation of the balloon and occlusion of the main lumen with the tip of the occlusion device allowed for intraarterial infusion chemotherapy and/or embolization of the target artery via the side hole. RESULTS: Successful intraarterial infusion chemotherapy and/or embolization with the microballoon catheter was performed in all patients with no complications. CONCLUSIONS: The newly developed microballoon catheter achieves intraarterial infusion chemotherapy and/or embolization without the need for superselective catheterization.	bladder
Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer.	miRNAs are small, non-coding RNAs that play important roles in various biological processes. The aims of our study were to investigate whether cell-free miRNAs can be measured in urine samples and might be an accurate biomarker of bladder cancer. Datasets of GSE20418 and GSE19717 were used for analysis, and two miRNAs, miR-145 and miR-200a, were selected for study. A total of 207 patients with primary transitional cell carcinoma of the urinary bladder and 144 healthy normal controls were enrolled. Using quantitative PCR, the levels of miR-145 and miR-200a in urine were measured and compared with the clinicopathological features of bladder cancer. According to our experiments, cell-free miRNAs were present in urine and were stable. Assessment of miR-145 levels was able to distinguish bladder cancer patients from non-cancer controls (77.8% sensitivity and 61.1% specificity for NMIBC, AUC 0.729; 84.1 and 61.1% for MIBC, respectively, AUC 0.790) and showed good correlation with grade (p=0.048). In addition, miR-200a was shown to be an independent predictor of NMIBC recurrence by multivariate analysis (OR 0.449, 95% CI 0.239‑0.842, p=0.013). A higher risk of recurrence was observed among patients with a lower miR-200a level compared to patients with higher miR-200a levels (log-rank test, p=0.040). Urinary cell-free miRNAs show promise as noninvasive biomarkers for diagnosis and recurrence of bladder cancer.	bladder
Application of AAPM TG 119 to volumetric arc therapy (VMAT).	The purpose of this study was to create AAPM TG 119 benchmark plans for volumetric arc therapy (VMAT) and to compare VMAT plans with IMRT plan data. AAPM TG 119 proposes a set of test clinical cases for testing the accuracy of IMRT planning and delivery system. For these test cases, we generated two treatment plans, the first plan using 7-9 static dMLC IMRT fields and a second plan utilizing one- or two-arc VMAT technique. Dose optimization and calculations performed using 6 MV photons and Eclipse treatment planning system. Dose prescription and planning objectives were set according to the TG 119 goals. Plans were scored based on TG 119 planning objectives. Treatment plans were compared using conformity index (CI) for reference dose and homogeneity index (HI) (for D(5)-D(95)). For test cases prostate, head-and-neck, C-shape and multitarget prescription dose are 75.6 Gy, 50.4 Gy, 50 Gy and 50 Gy, respectively. VMAT dose distributions were comparable to dMLC IMRT plans. Our planning results matched TG 119 planning results. For treatment plans studied, conformity indices ranged from 1.05-1.23 (IMRT) and 1.04-1.23 (VMAT). Homogeneity indices ranged from 4.6%-11.0% (IMRT) and 4.6%-10.5% (VMAT). The ratio of total monitor units necessary for dMLC IMRT to that of VMAT was in the range of 1.1-2.0. AAPM TG 119 test cases are useful to generate VMAT benchmark plans. At preclinical implementation stage, plan comparison of VMAT and IMRT plans of AAPM TG 119 test case allowed us to understand basic capabilities of VMAT technique.	bladder